The purpose of this application is to secure funding that will provide salary support for the named PI. The rationale for the application is based on the applicants demonstrated progression from student to Post-doctoral Fellow to Assistant Professor. This Progression has recently resulted in the acquisition of significant external funding and independent investigator status. The K02 Award will provide the applicant with the necessary funding to achieve both her short- and long-term goals which are respectively; to further develop her research expertise, publication record, and research funding; and to become an established investigator, with a strong independent research program. The candidates position at the University of Colorado Health Sciences Center, places her in an excellent environment to develop her research career. Important resources include the General Clinical Research Center, Clinical Nutrition Research Unit and Center for Human Nutrition. The studies proposed in this application aim to better understand gender differences in metabolism that relate to the development and/or protection against disease. Specific Aim #1 will determine the effects of epinephrine and norepinephrine on rates of lipolysis and glucose production in males and females. This will utilize the pancreatic clamp technique in conjunction with catecholamine infusions and stable isotope measurements. Specific Aim #$2 will determine if males and females differ in their ability to remove exogenous lipid from the circulation and whether there are gender differences in the ability of insulin to suppress endogenous very-low density lipoprotein triglyceride (VLDL-TG) and VLDL apolipoprotein-B (apo B) secretion,. Lipid clearance will be assessed in response to an intravenous fat tolerance test. Relative changes in VLDL-TG and apo B secretion will be measured following the radioactive labeling of VLDL-TG and stable isotope labeling of hepatic apo B. Measurement of VLDL-TG and apo B kinetics will be made under basal and hyperinsulinemic-euglycemic conditions. Specific Aim #3 will determine gender differences in the effects of acute exercises on meal lipid and carbohydrate metabolism. This will be achieved by the addition of radioactive and stable isotopes to a liquid meal and follow post-prandial tracer and nutrient partitioning, with and without, preceding exercise. These studies will further our understanding of the metabolic basis for disease in males and females and begin to identify gender specific effects of interventions.